DESCRIPTION: Pain management has been identified as a priority area in VA clinical care, and chronic back pain is a leading cause of disability for US veterans. The role in back pain of psychiatric disorders such as post- traumatic stress disorder (PTSD) has not been well studied in Veterans. For example, while there is a high co-occurrence of PTSD with chronic pain in Veterans, it remains unknown whether PTSD is a risk factor for the development of pain, or whether this co-occurrence is due to other factors such as shared familial predispositions. In addition, there have been no studies to date examining the genomics of back pain in Veterans. We propose a study of back pain in older Veterans who are members of the Vietnam Era Twin (VET) Registry. The Registry is comprised of 7369 male-male twin pairs, both of whom served in the military during the Vietnam conflict (1964-1975). We will capitalize on the rich data available in the Registry, and the recently completed study entitled, 'CSP 569: A Twin Study of the Course and Consequences of PTSD in Vietnam Era Veterans'. Our project consists of 3 interrelated components. First, we will analyze detailed information on PTSD and back pain from amongst the 7332 veterans who participated in CSP 569. Second, we will follow 171 MZ twin pairs who are discordant for PTSD symptoms, but are concordant for absence of back pain at baseline, for the occurrence of back pain. The longitudinal MZ co-twin design allows examination of the effect of an exposure while controlling for shared genetics and family environment. Third, we will conduct an epigenome-wide association study (EWAS) identifying differentially methylated regions (DMRs) associated with prevalent chronic back pain and back pain risk factors using recently acquired biospecimens from the VET Registry Biorepository. We will further cross-reference identified DMRs with existing databases of genes associated with known pain mechanisms, and conduct pathway analyses to identify specific biological networks which may be implicated in the production of pain. The candidate, Dr. Pradeep Suriyaarachchi, MD, MS is a physiatrist with subspecialty training in Pain Medicine and clinical expertise in back pain management. His career goal is to become an independent VA Investigator conducting epidemiologic research focused on the prevention of back pain, and improving function for Veterans with chronic back pain. His background is in clinical epidemiology, but he seeks to gain training in contemporary genetic epidemiology, genomics, and bioinformatics, in order to gain insights into the etiology of back pain, and to develop new interventions for back pain and related disability. He has assembled an outstanding mentorship team under the leadership of primary mentor Dr. Edward Boyko, MD, MPH. This mentorship team includes renowned experts in clinical epidemiology, genetic epidemiology, genomics, and bioinformatics, as well as the clinical domains of back pain and rehabilitation. The CDA-2 will allow Dr. Suriyaarachchi the structured coursework, mentorship, and applied learning needed to acquire new research skills in genetic epidemiology and genomics. Structured learning experiences will include formal coursework and seminars, regular local conferences, and attendance at scientific meetings. He will take advantage of key local resources to carry out the proposed research and training in the centers where his mentors are based, including the VA Seattle Epidemiologic Research and Information Center (where he is an investigator), the VET Registry, and the University of Washington's Department of Genome Sciences and Comparative Effectiveness, Cost, and Outcomes Research Center (which specializes in back pain research). This outstanding local environment will help ensure Dr. Suriyaarachchi's success.